Department of Behavioral Science, University of Kentucky College of Medicine, 140 Medical Behavioral Science Building, Lexington, KY 40536-0086, USA.
Psychopharmacology (Berl). 2013 Jul;228(2):255-62. doi: 10.1007/s00213-013-3031-y. Epub 2013 Feb 21.
Tapentadol is a novel analgesic that activates mu-opioid receptors and blocks norepinephrine reuptake. There is very little information available regarding the non-analgesic pharmacodynamic effects of tapentadol.
This outpatient study evaluated the physiological, subject-rated, and performance effects of therapeutic doses of tapentadol compared to two control drugs in humans.
This double-blind, within-subject study examined the effects of oral placebo, tapentadol (25, 50, and 75 mg), tramadol (50, 100, and 150 mg), and hydromorphone (2, 4, and 6 mg). Nine occasional opioid users completed the study. Pharmacodynamic drug effects were measured before and for 6 h after drug administration.
All three doses of the tested drugs produced comparable, time-dependent decreases in pupil diameter, but the effects were generally not dose dependent. The high dose of tapentadol, as well as all three doses of tramadol and hydromorphone, increased positive subject-rated effects (e.g., "Good Effects" and "Like the Drug") as a function of time. Only tramadol increased negative subject-rated effects (e.g., "Bad Effects" and "Nauseous"); however, these were of low magnitude.
The highest tested dose of tapentadol produced a profile of positive effects comparable to that of hydromorphone, whereas tramadol produced positive and negative subject-rated effects. The mixed findings for tramadol are consistent with previous findings indicating that it has a distinct profile of effects relative to prototypic opioids. Future research should examine the effects of higher tapentadol doses, as well as the factors contributing to the different subject-rated profile of effects observed for tramadol relative to tapentadol and hydromorphone.
盐酸他喷他多是一种新型的阿片类镇痛药，能够同时激活μ-阿片受体和抑制去甲肾上腺素再摄取。目前，关于盐酸他喷他多的非镇痛药效动力学效应的信息非常有限。
本门诊研究旨在评估治疗剂量的盐酸他喷他多与两种对照药物在人体中的生理、主观和行为表现效应。
本双盲、自身对照研究考察了口服安慰剂、盐酸他喷他多（25、50 和 75mg）、曲马多（50、100 和 150mg）和氢吗啡酮（2、4 和 6mg）的效应。9 名偶尔使用阿片类药物的患者完成了这项研究。在给药前和给药后 6 小时内测量药效动力学药物效应。
测试药物的所有三个剂量均产生了类似的、时间依赖性的瞳孔直径减小，但效应通常与剂量无关。高剂量的盐酸他喷他多以及曲马多和氢吗啡酮的所有三个剂量均随着时间的推移增加了阳性主观效应（例如“良好效应”和“喜欢药物”）。只有曲马多增加了阴性主观效应（例如“不良效应”和“恶心”）；然而，这些效应的程度较低。
测试的最高剂量的盐酸他喷他多产生的积极效应与氢吗啡酮相当，而曲马多则产生了积极和消极的主观效应。曲马多的混合发现与先前的发现一致，表明它与典型阿片类药物具有明显不同的效应特征。未来的研究应该考察更高剂量的盐酸他喷他多的效应，以及导致曲马多相对于盐酸他喷他多和氢吗啡酮观察到的不同主观效应特征的因素。
